Calcium-triggered exit of F-actin and IP(3) 3-kinase A from dendritic spines is rapid and reversible

Eur J Neurosci. 2006 Nov;24(9):2491-503. doi: 10.1111/j.1460-9568.2006.05125.x.

Abstract

The structure of the actin cytoskeleton in dendritic spines is thought to underlie some forms of synaptic plasticity. We have used fixed and live-cell imaging in rat primary hippocampal cultures to characterize the synaptic dynamics of the F-actin binding protein inositol trisphosphate 3-kinase A (IP3K), which is localized in the spines of pyramidal neurons derived from the CA1 region. IP3K was intensely concentrated as puncta in spine heads when Ca(2+) influx was low, but rapidly and reversibly redistributed to a striated morphology in the main dendrite when Ca(2+) influx was high. Glutamate stimulated the exit of IP3K from spines within 10 s, and re-entry following blockage of Ca(2+) influx commenced within a minute; IP3K appeared to remain associated with F-actin throughout this process. Ca(2+)-triggered F-actin relocalization occurred in about 90% of the cells expressing IP3K endogenously, and was modulated by the synaptic activity of the cultures, suggesting that it is a physiological process. F-actin relocalization was blocked by cytochalasins, jasplakinolide and by the over-expression of actin fused to green fluorescent protein. We also used deconvolution microscopy to visualize the relationship between F-actin and endoplasmic reticulum inside dendritic spines, revealing a delicate microorganization of IP3K near the Ca(2+) stores. We conclude that Ca(2+) influx into the spines of CA1 pyramidal neurons triggers the rapid and reversible retraction of F-actin from the dendritic spine head. This process contributes to changes in spine F-actin shape and content during synaptic activity, and might also regulate spine IP3 signals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Actins / ultrastructure*
  • Animals
  • Calcium / metabolism*
  • Cells, Cultured
  • Cytoskeleton / ultrastructure
  • Dendritic Spines / metabolism
  • Dendritic Spines / ultrastructure*
  • Diagnostic Imaging
  • Endoplasmic Reticulum / metabolism
  • Glutamic Acid / metabolism
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Neuronal Plasticity / physiology*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Rats
  • Transfection

Substances

  • Actins
  • Glutamic Acid
  • Phosphotransferases (Alcohol Group Acceptor)
  • Inositol 1,4,5-trisphosphate 3-kinase
  • Calcium